Search Results (166)

The report examines food availability and demand in the Anthropocene era, exploring the connections between global population growth and carrying capacity through an extended version of Cohen’s Condorcet concept. It recalls the super-Malthus and Verhulst-type scalings, matched with the recently introduced analytic relative growth rate. It focuses particularly on the ongoing Fifth Industrial Revolution (IR) and its interaction with the concept of a sustainable civilization. In this context, the significance of innovative food preservation technologies that can yield high-quality foods with health-promoting features, while simultaneously increasing food quantities and reducing adverse environmental impacts, is discussed. To achieve this, high-pressure preservation and processing (HPP) can play a dominant role. High-pressure ‘cold pasteurization’, related to room-temperature processing, has already achieved a global scale. Its superior features are notable and are fairly correlated with social expectations of a sustainable society and the technological tasks of the Fifth Industrial Revolution. The discussion is based on the authors’ experiences in HPP-related research and applications. The next breakthrough could be HPP-related sterilization. The innovative HPP path, supported by the colossal barocaloric effect, is presented. The mass implementation of pressure-related sterilization could lead to milestone societal, pro-health, environmental, and economic benefits. Full article

Text2Cypher is a text-to-text task that converts natural language questions into Cypher queries. Recent research by Neo4j on Text2Cypher demonstrates that fine-tuning a baseline language model (a pretrained and instruction-tuned generative model) using a comprehensive Text2Cypher dataset can effectively enhance query generation performance. However, the improvement is still insufficient for effectively learning the syntax and semantics of complex natural texts, particularly when applied to unseen Cypher schema structures across diverse domains during training. To address this challenge, we propose a novel refinement training method based on baseline language models, employing reinforcement learning with Group Relative Policy Optimization (GRPO). This method leverages extracted semantic information, such as key-value properties and triple relationships from input texts during the training process. Experimental results of the proposed refinement training method applied to a small-scale baseline language model (SLM) like Qwen2.5-3B-Instruct demonstrate that it achieves competitive execution accuracy scores on unseen schemas across various domains. Furthermore, the proposed method significantly outperforms most baseline LMs with larger parameter sizes in terms of Google-BLEU and execution accuracy scores over Neo4j’s comprehensive Text2Cypher dataset, with the exception of colossal LLMs such as GPT4o, GPT4o-mini, and Gemini. Full article

Recent outbreaks caused by hMPXV, especially hMPXV lineages/sub-lineages, represent public health threats necessitating stringent prophylactic measures to ameliorate their colossal impact. The current study annotated the EEV form of hMPXV’s target proteins to formulate a reverse vaccinology-dependent hMPXV multiepitope vaccine. Epitope determination, followed by vaccine formulation, was undertaken. The promising formulation was validated for its potential to trigger immune responses immunoinformatically. The MPXV-1-Beta formulation was characterised as a promising candidate based on antigenicity score, physicochemical properties, solubility score, ProSA Z-score, and Ramachandran plot. Docking, normal mode analysis, and molecular dynamic simulation of MPXV-1-Beta with TLRs and MHCs authenticated rigid docking and its efficacy in enhancing immune receptor activation under physiological conditions. MPXV-1-Beta was discerned to trigger a sustained immune response (IR) with a broader average population coverage of 97.526, SD = 12.44. The proposed MPXV-1-Beta candidate showed significant potential. The findings of this study provide a preliminary framework for developing an efficacious hMPXV vaccine; however, extensive in vitro, in vivo, and clinical evaluations are required to substantiate the computational insights. Full article

Diluted magnetic semiconductors (DMSs) represent a significant area of interest for research and applications in spintronics. Recently, DMSs derived from BaZn₂As₂ have garnered significant interest due to the record Curie temperature (T_C) of 260 K. However, the influence of doping on their magnetic evolution and transport characteristics has not been thoroughly investigated. This study aims to fill this gap through susceptibility and magnetization measurements, electric transport analysis, and muon spin relaxation and rotation (µSR) measurements on (Ba_1−xRb_x)(Zn_1−yMn_y)₂As₂ (0.1 ≤ x, y ≤ 0.25, BRZMA). Key findings include the following: (1) BRZMA showed a maximum T_C of 138 K, much lower than (Ba,K)(Zn,Mn)₂As, because of a reduced carrier concentration. (2) A substantial electromagnetic coupling is evidenced by a negative magnetoresistance of up to 34% observed in optimally doped BRZMA. (3) A 100% static magnetic ordered volume fraction is achieved in the low-temperature region, indicating a homogeneous magnet. (4) Furthermore, a systematic and innovative methodology has been initially proposed, characterized by clear step-by-step instructions aimed at enhancing T_C, grounded in robust experimental findings. The findings presented provide valuable insights into the spin–charge interplay concerning magnetic and electronic transport properties. Furthermore, they offer clear direction for the investigation of higher T_C DMSs. Full article

The recent birth of genetically modified canids phenotypically resembling the extinct dire wolf (Aenocyon dirus) was hailed as a landmark in synthetic biology. Using genome editing and cloning, the biotech company Colossal Biosciences created three such animals from gray wolf cells, describing the project as an effort in “functional de-extinction”. This case raises significant questions regarding animal welfare, moral justification, and regulatory governance. We used the five domains model framework to assess the welfare risks for the engineered animals, the surrogate mothers used in reproduction, and other animals potentially affected by future reintroduction or escape scenarios. Ethical implications are examined through utilitarian, deontological, virtue, relational, and environmental ethics. Our analysis suggests that the project suffers from ontological ambiguity: it is unclear whether the animals created are resurrected species, hybrids, or novel organisms. While the current welfare of the engineered animals may be manageable, their long-term well-being, particularly under rewilding scenarios, is likely to be compromised. The moral arguments for reviving long-extinct species are weak, particularly in cases where extinction was not anthropogenic. Legally, the current EU frameworks lack the clarity and scope to classify, regulate, or protect genetically engineered extinct animals. We recommend that functional de-extinction involving sentient beings be approached with caution, supported by revised welfare tools and regulatory mechanisms. Full article

Novel diluted magnetic semiconductors derived from BaZn₂As₂ are of considerable importance owing to their elevated Curie temperature of 260 K, the diversity of magnetic states they exhibit, and their prospective applications in multilayer heterojunctions. However, the transition from the intrinsic semiconductor BaZn₂As₂ (BZA) to its doped compounds has not been extensively explored, especially in relation to the significant intermediate compound Ba(Zn,Mn)₂As₂ (BZMA). This study aims to address this gap by performing susceptibility and magnetization measurements, in addition to electronic transport analyses, on these compounds in their single crystal form. Key findings include the following: (1) carriers can significantly modulate the magnetism, transitioning from a non-magnetic BZA to a weak magnetic BZMA, and subsequently to a hard ferromagnet (Ba,K)(Zn,Mn)₂As₂ with potassium (K) doping to BZMA; (2) two distinct sets of metal-insulator transitions were identified, which can be elucidated by the involvement of carriers and the emergence of various magnetic states, respectively; and (3) BZMA exhibits colossal negative magnetoresistance, and by lanthanum (La) doping, a potential n-type (Ba,La)(Zn,Mn)₂As₂ single crystal was synthesized, demonstrating promising prospects for p-n junction applications. This study enhances our understanding of the magnetic interactions and evolutions among these compounds, particularly in the low-doping regime, thereby providing a comprehensive physical framework that complements previous findings related to the high-doping region. Full article

Background: hMPXV poses a major public health risk due to its human-to-human transmissibility, severe complications, especially in immunocompromised individuals, and global spread, necessitating effective surveillance and stringent prophylactic measures to mitigate its colossal impact. Objective: The study aimed to annotate hMPXV(IMV) proteins to propose a potential reverse vaccinology-based vaccine against hMPXV. Methods: The target MPXV(IMV) protein’s sequences, formatted in FASTA, were sourced from genome/proteome databases (BV-BRC and UniProt) (accessed on 6 November 2024), followed by CD-Hit-based redundancy removal. Epitope prediction for B-cells (lymphocytes), cytotoxic T-cells or cytotoxic T-lymphocytes (CTLs), and helper T-cells (HTLs) was executed using ABCpred, IEDB’s ANNs 4.0, and an artificial neural network-based alignment tool (NN-align 2.3)/ML-based tool (NetMHCII 2.3). Various immunoinformatics filters (antigenicity, toxicity, and allergenicity) were applied to substantiate the potency and safety of the formulated vaccine candidate. The constructed vaccine’s physiochemical and structural features (secondary and tertiary), with structural stability (confirmed by molecular docking followed by dynamic simulation with TLRs (TLR4 & TLR2) and MHCs), were determined. Additionally, cloning (using pET-28a(+) vector) was conducted to verify the vaccine’s expression potential and translation efficiency. The construct’s population coverage was also ascertained. Results: The MPXV-2-Beta vaccine constructs, of the six initially designed constructs, was identified as the most promising candidate, signifying nonallergenic profile and nontoxic features, with a predicted antigenicity score (PAS) = 0.7202, 407 residues, a molecular weight of 43,102.1 Da, pI of 9.2, and favorable stability parameters (AI: 65.65, GRAVY: −0.597, I-i: 25.92). It showed high solubility (score: 0.942). The ProSA Z-score of −9.38 confirmed the structural stability, reliability, and precision of the MPXV-2-Beta 3D model, which is comparable to experimental structures. Furthermore, 98.8% of all the residues nested within favored or allowed regions in a critical Ramachandran plot signified the model’s exceptional structural integrity and quality. Docking and dynamic simulation of MPXV-2-Beta with TLRs (TLR4 & TLR2) and MHCs demonstrated stiffer docking stability (strong polar and nonpolar interaction) and negative eigenvalue value (during dynamic simulation), suggesting its ability to enhance immune receptor activation under physiological conditions. MPXV-2-Beta was predicted to trigger a robust immune response (IR) with comprehensive world population coverage (98.55%, SD = 10.41). Conclusions: Based on the evaluated parameters, the MPXV-2-Beta designed in this study exhibited significant potential as an effective candidate against hMPXV. This study establishes a foundation for developing an efficient vaccine against hMPXV, requiring further experimental and clinical validation to confirm computational findings. Full article

The traditional chemical safety management method mainly relies on manual inspection and empirical judgment, which is incompetent in the face of the increasingly complex production environment and colossal data volume, and there is an urgent need to apply efficient modern emerging technologies to strengthen the safety management of chemical production sites. Therefore, this dissertation researches chemical safety risk factor identification and analysis predicated on improved LDA topic model and Bayesian network. Thirty-three main risk factors are obtained by constructing the LDA topic model, text mining, and thematic analysis of chemical safety accident cases and combining them with the socio-technical system accident model. The correlation and causal relationship between risk factors were revealed based on association rule mining and Bayesian network analysis. Sensitivity and critical causal path analyses were utilized to indicate the possible paths and vital aspects of accident development. The results show that the text mining LDA topic model proposed in the dissertation performs well in analyzing accident reports and can effectively solve the problems of insufficient analyzing ability and high subjectivity of traditional methods. The research method of the thesis can efficiently extract the keywords of accident reports and reveal the correlation and causality between risk factors. Full article

Manganese oxides (manganites) are among the most studied materials in condensed matter physics due to the famous colossal magnetoresistance and very rich phase diagrams characterized by strong competition between ferromagnetic (FM) metallic and antiferromagnetic (AFM) insulating phases. One of the key questions that remains open even after more than thirty years of intensive research is the exact conductivity mechanism in insulating as well as in metallic phases and its relation to the corresponding magnetic structure. In order to shed more light on this problem, here, we report magnetotransport measurements on sintered nanocrystalline samples of the very poorly explored manganites ${\mathrm{Ca}}_{1-x}{\mathrm{Gd}}_x{\mathrm{MnO}}_3$ with $x=0.05$ and $x=0.10$, in the temperature range 2–300 K, and in magnetic fields up to 16 T. Our results indicate that both compounds at low temperatures exhibit metallic behavior with a peculiar resistivity upturn and a large negative magnetoresistance. We argue that such behavior is consistent with a Kondo-like scattering on Gd impurities coupled with the percolation of FM metallic regions within insulating AFM matrix. Full article

The incorporation of waste ground glass powder (GGP) in concrete as a partial replacement of cement offers significant environmental benefits, such as reduction in CO₂ emission from cement manufacturing and decrease in the use of colossal landfill space. However, concrete is a heterogeneous material, and the prediction of its accurate compressive strength is challenging due to the inclusion of several non-linear parameters. This study explores the utilization of different machine learning (ML) algorithms: linear regression (LR), ElasticNet regression (ENR), a K-Nearest Neighbor regressor (KNN), a decision tree regressor (DT), a random forest regressor (RF), and a support vector regressor (SVR). A total of 187 sets of pertinent mix design experimental data were collected to train and test the ML algorithms. Concrete mix components such as cement content, coarse and fine aggregates, the water–cement ratio (W/C), various GGP chemical properties, and the curing time were set as input data (X), while the compressive strength was set as the output data (Y). Hyperparameter tuning was carried out to optimize the ML models, and the results were compared with the help of the coefficient of determination (R²) and root mean square error (RMSE). Among the algorithms considered, SVR demonstrates the highest accuracy and predictive capability with an R² value of 0.95 and RMSE of 3.40 MPa. Additionally, all the models exhibit R² values greater than 0.8, suggesting that ML models provide highly accurate and cost-effective means for evaluating and optimizing the compressive strength of GGP-incorporated sustainable concrete. Full article

TNF-α is a pro-inflammatory cytokine that plays a pivotal role in the regulation of immune responses. It is predominantly produced by activated macrophages, although other cell types, such as T lymphocytes and NK cells, also contribute to its secretion. TNF-α participates in various physiological processes, including cell proliferation and differentiation. Moreover, TNF-α has been implicated in the pathogenesis of numerous inflammatory and autoimmune disorders. Recent studies have highlighted the important role of TNF-α in neuropathic pain, a complex and frequently disabling condition caused by nerve injury or dysfunction. Increased TNF-α levels in the nervous system have been associated with the onset of neuropathic pain, contributing to neuronal sensitization and alterations in pain signaling pathways. This study supports the idea that TNF-α connects the immune system with the nervous system, thereby supporting our understanding of the neuroimmune interface of pain and bringing a potential treatment against neuropathic pain: targeting TNF-α. Anti-TNF-α antibody administration reduces pain behaviors and neuroinflammation in preclinical animal models. Simultaneously, clinical trials are evaluating the safety and efficacy of anti-TNF-α treatments, with preliminary results indicating promising outcomes in patients experiencing neuropathic pain. Here, targeting TNF-α goes beyond its conventional spectrum of inflammatory pathologies and initiates a new mechanism-based approach to defining neuropathic pain, thereby improving the quality of life of the individuals affected and bringing together an area of colossal unmet clinical need. Full article

The Nigeria–Biafra war (1967–1970) has been regarded as the first major civil war in post-colonial Africa, with an attendant and colossal loss of lives, property, and infrastructure. There are many representations of memories of the war in fiction, non-fiction, symbols, memoires, and post-war relics (usually found in museums) but the role of personal naming practices has been largely neglected in the literature and social narratives of the war history. This article, therefore, aims to investigate the performance of personal names as significant memorial sites that convey trajectories of post-traumatic experiences of the war and the desire for healing and reconciliation. The study adopts the theoretical lens of the socio-onomastic analytic framework, which explores the social contexts in which names are given and used. Drawing on ethnographic data sourced mainly from personal histories and semi-structured interviews with 30 participants in Nsukka (Enugu State) and Owerri (Imo State) in southeastern Nigeria, we argue that personal naming practices form essential elements of the war memory, which positively impact self-recovery and meaningful connection with the people. The study concludes that war-related names are based on name-givers’ lived experiences and life-altering situations that greeted the war and are useful in sharing and preserving collective memory of the war. Full article

The marine environment, covering over 70% of the Earth’s surface, serves as a reservoir of bioactive molecules, including peptides and proteins. Due to the unique and often extreme marine conditions, these molecules exhibit distinctive structural features and diverse functional properties, making them promising candidates for therapeutic applications. Marine-derived bioactive peptides, typically consisting of 3 to 40 amino acid residues—though most commonly, 2 to 20—are obtained from parent proteins through chemical or enzymatic hydrolysis, microbial fermentation, or gastrointestinal digestion. Like peptides, protein hydrolysates from collagen, a dominant protein of such materials, play an important role. Peptide bioactivities include antioxidant, antihypertensive, antidiabetic, antimicrobial, anti-inflammatory, anticoagulant, and anti-cancer effects as well as immunoregulatory and wound-healing activities. These peptides exert their effects through mechanisms such as enzyme inhibition, receptor modulation, and free radical scavenging, among others. Fish, algae, mollusks, crustaceans, microbes, invertebrates, and marine by-products such as skin, bones, and viscera are some of the key marine sources of bioactive proteins and peptides. The advancements in the extraction and purification processes, e.g., enzymatic hydrolysis, ultrafiltration, ion-exchange chromatography, high-performance liquid chromatography (HPLC), and molecular docking, facilitate easy identification and purification of such bioactive peptides in greater purity and activity. Despite their colossal potential, their production, scale-up, stability, and bioavailability are yet to be enhanced for industrial applications. Additional work needs to be carried out for optimal extraction processes, to unravel the mechanisms of action, and to discover novel marine sources. This review emphasizes the enormous scope of marine-derived peptides and proteins in the pharmaceutical, nutraceutical, cosmeceutical, and functional food industries, emphasizing their role in health promotion and risk reduction of chronic diseases. Full article

The cancer chemotherapy regimen of a taxane and platinum combination was developed more than forty years ago, yet remains the cornerstone of treatment for several major cancer types today. Although many new agents targeting cancer genes and pathways have been developed and evaluated, none have been sufficient to replace the long-established taxane/platinum combination. This leads us to ponder why, after four decades of colossal efforts, multiple discoveries, and tremendous advances in understanding gene mutations and biology, the development of conceptually superior targeted therapies has not yet achieved overwhelming success in replacing cytotoxic chemotherapy. The concept of targeted therapy is based on the idea that blocking the altered pathway(s) crucial for cancer development (and maintenance), the disturbance in cellular signaling, metabolism, and functions will make the targeted cancer cells unfit and trigger programmed cell death in cancer cells, but without the significant side effects that limit chemotherapy. We propose that the lack of anticipated triumphs of targeted therapy stems from the desensitization of programmed cell death pathways during neoplastic transformation and malignant progression of cancer cells. This renders the targeting drugs largely ineffective at killing cancer cells and mostly insufficient in clinical implements. Recent advances in understanding suggest that, in contrast to targeted therapies, taxanes and platinum agents kill cancer cells by physical rupturing nuclear membranes rather than triggering apoptosis, making their effect independent of the intrinsic cellular programmed cell death mechanism. This new recognition of the non-programmed cell death mechanism in the success of chemotherapeutic agents, such as taxanes and platinum, may inspire oncologists and cancer researchers to focus their efforts more productively on developing effective non-programmed cell death cancer therapies to replace or significantly improve the application of the current standard taxane/platinum regimens. Full article

The COVID-19 pandemic, driven by the high transmissibility and immune evasion caused by SARS-CoV-2 and its variants (e.g., Alpha, Delta, Omicron), has led to massive casualties worldwide. As of November 2024, the International Committee on Taxonomy of Viruses (ICTV) has identified 14,690 viral species across 3522 genera. The increasing infectious and resistance to FDA and EMA-approved antivirals, such as 300-fold efficacy reduction in Nirmatrelvir against the SARS-CoV-2 3CLpro, highlight the need for mutation-stable antivirals, likewise targeting the essential host proteins like kinases, heat shock proteins, lipid metabolism proteins, immunological pathway proteins, etc. Unlike direct-acting antivirals, HDAs reduce the risk of resistance by targeting conserved host proteins essential for viral replication. The proposal for repurposing current FDA-approved drugs for host-directed antiviral (HDA) approach is not new, such as the Ouabain, a sodium-potassium ATPase inhibitor for herpes simplex virus (HSV) and Verapamil, a calcium channel blocker for influenza A virus (IAV), to name a few. Given the colossal potential of the mutation-stable HDA approach to exterminate the virus infection, it has been increasingly studied on SARS-CoV-2. This review aims to unravel the interaction between viruses and human hosts and their successfully proposed host-directed antiviral approach to provide insight into an alternative treatment to the rampant mutation in SARS-CoV-2. The benefits, limitations, and potential of host protein-targeted antiviral therapies and their prospects are also covered in this review. Full article